Figure 4. Integration of cargo and targeting signals by the cargo recognition complex.

a, The Vps26:Vps29:Vps35 complex is predicted to align roughly parallel to the membrane (green line at bottom), such that its multiple SNX ⁴, ¹⁵ and cargo-binding sites ²⁵ cooperatively interact. The arrows mark the central region about which Vps35 is proposed to flex so as to interact with cargo embedded in curved membranes. Binding sites that have been mapped to individual residues within crystallized components are shown in blue. Binding sites that have been mapped to regions of Vps35 or to as yet uncrystallized portions of Vps35 are marked by red bars aligned with the region of interest. Binding sites for yeast cargo proteins are not necessarily conserved in human Vps35, however the overall architecture of the yeast and other orthologous complexes is proposed to be very similar to the human complex. b, Schematic rendering of a speculative model for the retromer coat on a tubular vesicle, colored as above, with the SNX dimer in purple.